Table 2.
Treatment protocols and outcomes for studies investigating procedures (debridement, photodynamic therapy, or lasers) in combination with medication for onychomycosis treatment.
| Study | Combination Therapy | # Subjects Completed | Combination Treatment Protocol | Monotherapy Treatment Protocol | Combination Treatment Rates, % | Monotherapy Treatment Rates, % | Difference between Groups | Adverse Effects Combination Therapy, n, % | Adverse Effects Monotherapy, n, % |
|---|---|---|---|---|---|---|---|---|---|
| Zhang, J. et al., 2016 [33] † | Laser & topical amorolfine | 9 | 2940-nm fractional Er:YAG laser once weekly at weeks 1, 2, 3, 4, 8, & 12 + 5% amorolfine lacquer twice weekly × 12 weeks | Amorolfine 5% lacquer twice weekly × 12 weeks | 12 weeks M: 70 24 weeks M: 75 |
12 weeks M: 25 24 weeks M: 20 |
12 weeks: p = 0.01 * 24 weeks: p = 0.001 * |
Not specified by group (n = 3 total) | Not specified by group (n = 3 total) |
| Bunyaratevej, S. et al., 2020 [34] † | Laser & topical amorolfine | 60 | (A) Long-pulsed Nd:YAG 1064-nm laser × 4 sessions at 1 month intervals + topical amorolfine nail lacquer × 3 months | (B) Nd:YAG 1064-nm laser × 4 sessions at 1 month intervals (C) Topical amorolfine nail lacquer × 3 months |
3 months M: 65 C: 30 |
3 months M: 35 (B), 60 (C) C: 10 (B), 30 (C) |
M: p = 0.05 * (A vs. B) | N/a | N/a |
| Zhang, J. et al., 2021 [35] † | Laser & topical amorolfine | 78 | 2940-nm Er:YAG fractional laser × 6 treatments at weeks 1, 2, 3, 4, 8, & 12 + topical amorolfine 5% nail lacquer twice weekly × 12 weeks | Topical amorolfine 5% lacquer twice weekly × 12 weeks | Mild (A), moderate (B), severe (C) onychomycosis 12 weeks M: 100 (A), 63.64 (B), 7.69 (C) O: 2 (A), 6, (B) 4 (C) 24 weeks M: 100 (A), 66.67 (B), 7.79(C) O: 2 (A), 8 (B), 4 (C) |
Mild (A), moderate (B), severe (C) onychomycosis 12 weeks M: 84.62 (A), 38.24 (B), 8.33 (C) O: 1 (A), 3 (B), 7 (C) 24 weeks M: 61.54 (A), 35.29 (B), 4.17 (C) O: 1 (A), 4 (B), 8 (C) |
12 weeks M: p = 0.038 * (B) O: p = 0.037 * (A), p < 0.001 * (B) 24 weeks M: p = 0.046 * (A), p = 0.01 * (B) O: p = 0.002 * (A), p < 0.001 * (B) |
32, 84.213 | N/a |
| Bonhert, K. et al., 2019 [36] † | Laser & topical efinaconazole | 30 | 1064-nm Nd-YAG laser × 6 treatments spaced 4 weeks apart + topical efinaconazole 10% once daily × 48 weeks | Topical efinaconazole 10% once daily × 48 weeks | 48 weeks M: 90 52 weeks M: 92 |
48 weeks M: 70 52 weeks M: 86 |
Combined vs. monotherapy:
|
7, 46% | N/a |
| Li, Y. et al., 2016 [37] † | Laser & oral itraconazole | 19 | 1064-nm Nd:YAG laser once weekly × 8 weeks + 200 mg oral itraconazole twice daily × 1 week for 4 times | 1064-nm Nd:YAG laser once weekly × 8 weeks for 4 times | Mild/moderate (A), severe onychomycosis (B) 8 weeks E: 21 (A), 20 (B) 16 weeks E: 20 (A), 19 (B) 24 weeks E: 19 (A), 21 (B) |
Mild/moderate (A), severe onychomycosis (B) 8 weeks E: 17 (A), 13 (B) 16 weeks E: 17 (A), 14 (B) 24 weeks E: 19 (A), 11(B) |
A: p > 0.05 (8, 16, 24 weeks) B: p < 0.05 * (8 & 24 weeks), p > 0.05 (16 weeks) |
N/a | N/a |
| Hamed Khater, M. & Khattab, F.M. 2020 [38] † | Laser & oral itraconazole | 30 | 1064-nm long-pulsed Nd-YAG laser × 6 sessions (every 2 weeks × 3 months) + oral itraconazole 200 mg twice daily 1 week per month × 3 months | Oral itraconazole 200 mg twice daily 1 week per month × 3 months | C: Excellent: 66.6 Moderate: 6.6 Good: 20.1 Mild: 6.6 MR: Excellent: 13.3 Moderate: 40.6 Good: 13.3 Mild: 33.3 Mean OSI after treatment: 5.07 ± 4.15 |
C: Excellent: 13.3 Moderate: 33.3 Good: 40.1 Mild: 13.3 MR: Excellent: 13.3 Moderate: 40.1 Good: 13.3 Mild: 33.3 Mean OSI after treatment: 6.67± 3.60 |
Overall C: p = 0.001 * Mean OSI: p < 0.01 * |
N/a | N/a |
| Zaki, A.M. et al., 2020 [39] † | Laser & topical tioconazole | 120 | Fractional CO2 laser × 5 sessions at 3-weeks intervals + topical tioconazole 28% applied twice daily × 16 weeks | (A) Fractional CO2 laser × 5 sessions at 3-weeks intervals × 16 weeks (B) Topical tioconazole 28% applied twice daily × 16 weeks |
C: 55 PS: 60 KOH turned negative: 80 Culture turned negative: 70 |
C: 30 (A), 25 (B) PS: 40 (A), 30 (B) KOH turned negative: 60 (A), 55 (B) Culture turned negative: 50 (B), 30 (C) |
C: p < 0.001 * PS: p = 0.007 * KOH turned negative: p = 0.001 * Culture turned negative: p < 0.001 * |
N/a | N/a |
| Zhou, B.R. et al., 2016 [40] † | Laser & topical luliconazole | 60 | Fractional CO2 laser × 12 sessions at 2-weeks intervals + luliconazole 1% cream daily × 6 months | Fractional CO2 laser × 12 sessions at 2-week intervals × 6 months | 3 months C: 69.6 6 months C: 73.0 3 months after last treatment M: 69.6 |
3 months C: 50.9 6 months C: 52.8 3 months after last treatment M: 57.4 |
C: p = 0.004 * (3 months), p = 0.002 * (6 months) M: p = 0.006 * |
N/a | N/a |
| Xu, Y. et al., 2014 [41] † | Laser & oral terbinafine | 53 | Long-pulsed 1064-nm Nd:YAG laser treatment once weekly + oral terbinafine 250 mg daily × 24 weeks | (A) Long-pulsed 1064-nm Nd:YAG laser treatment once weekly × 24 weeks (B) Oral terbinafine 250 mg daily × 24 weeks |
4 weeks M: 31.03 C: 20.69 8 weeks M: 68.97 C: 51.72 12 weeks M: 93.10 C: 86.21 16 weeks M: 96.55 C: 93.10 24 weeks M: 100 C: 96.55 |
4 weeks M: 0 (A), 10 (B) C: 0 (A), 0 (B) 8 weeks M: 16.13 (A), 36.67 (B) C: 3.23 (A), 16.67 (B) 12 weeks M: 35.48 (A), 70 (B) C: 29.03 (A), 63.33 (B) 16 weeks M: 48.39 (A), 73.33 (B) C: 35.48 (A), 70 (B) 24 weeks M: 77.42 (A), 83.33 (B) C: 64.52 (A), 73.33 (B) |
M, C (combination vs. A & B): p < 0.05 * (all timepoints) |
N/a | 1, 6.3 (B) |
| Kim, T.I. et al., 2016 [42] † | Laser & topical naftifine HCl spray | 53 | 1064-nm Nd:YAG laser × 3 sessions at 4-week intervals + topical naftifine HCl spray daily × 24 weeks | (A) 1064-nm Nd:YAG laser × 3 sessions at 4-week intervals (B) Naftifine HCl spray daily × 24 weeks |
12 weeks C: 35.2 M: 14.1 24 weeks C: 40.8 M: 22.5 |
12 weeks C: 25.3 (A), 7.5 (B) M: 8.9 (A), 6.0 (B) 24 weeks C: 31.6 (A), 7.5 (B) M: 15.2 (A), 4.5 (B) |
C: p < 0.005 * (combination/A vs. B at 12 and 24 weeks) M: p < 0.005 * (combination/A vs. B at 24 weeks) |
N/a | N/a |
| Gilaberte, Y. et al., 2017 [43] | Methyl aminolevulinate photodynamic therapy & topical urea |
40 | Methyl aminolevulinate photodynamic therapy + urea 40% ointment × 3 sessions |
Placebo (red light) photodynamic therapy + urea 40% ointment × 3 sessions | M: 31.82 CO: 18.18 |
M: 11.1 CO: 31.82 |
M: p = 0.178 CO: p = 0.23 |
Pigmentation: 22, 100 Inflammation: 4, 18.2 Tinea pedis: 3, 13.64 |
Pigmentation: 15, 83.3 Inflammation: 0, 0 Tinea pedis: 2, 11.11 |
| Jennings, M.B. et al., 2006 [44] † | Debridement & oral terbinafine | 504 | Oral terbinafine 250 mg daily × 12 weeks + aggressive nail debridement | Oral terbinafine 250 mg daily × 12 weeks | 48 weeks C: 59.8 M: 67.5 CO: 37.8 |
48 weeks C: 51.4 M: 62.6 CO: 32.5 |
C: p = 0.023 * M: p > 0.05 CO: p > 0.05 |
Not specified by group (n = 116 total) | Not specified by group (n = 116 total) |
| Potter, L.P. et al., 2007 [45] † | Debridement & oral terbinafine | 504 | Oral terbinafine 250 mg daily × 12 weeks + aggressive nail debridement at baseline & weeks 6, 12, & 24 | Oral terbinafine 250 mg daily × 12 weeks | SF: 28.7 SB: 20.4 A: 25.5 PA: 20.7 OP: 28.2 S: 8.9 |
SF: 25.8 SB: 19.2 A: 23.4 PA: 20.7 OP: 28.2 S: 10.0 |
SF: p = 0.0395 * SB: p = 0.3783 A: p = 0.1543 PA: p = 0.9761 OP: p = 0.9897 S: p = 0.4040 TS: p = 0.0077 * |
N/a | N/a |
| Malay, D.S. et al., 2009 [46] † | Debridement & topical ciclopirox | 55 | Debridement at 3-month intervals × 9–12 months + topical ciclopirox 8% daily | Debridement at 3-month intervals × 9–12 months | M: 76.74 | M: 0 | M: p < 0.05 * | N/a | N/a |
| Shemer, A. et al., 2016 [47] † | Nail drilling, oral & topical terbinafine | 98 | (A) Nail drilling once at baseline + oral terbinafine 250 mg daily × 2 weeks + topical terbinafine 1% spray twice daily × 6 month (B) Nail drilling once at baseline + topical terbinafine 1% spray twice daily × 6 months |
Topical terbinafine 1% spray twice daily × 6 months | 10 weeks M: 14.3 (A), 2.4 (B) 16 weeks M: 35.7 (A), 6.3 (B) CN: 63.75 (A), 39.95 (B) 22 weeks M: 46.2 (A), 32.4 (B) CN: 59.38 (A), 52.39 (B) 28 weeks M: 47.1 (A), 34.2 (B) |
10 weeks M: 0.0 16 weeks M: 0.0 CN: 31.36 22 weeks M: 5.0 CN: 23.81 28 weeks M: 8.0 |
16 weeks CN: p = 0.028 * (A vs. C) 22 weeks CN: p = 0.005 * (A vs. C), p = 0.014 * (B vs. C) |
Not specified by group (n = 8 total) | Not specified by group (n = 8 total) |
A: appearance problems; C: clinical cure rate; CI: confidence interval; CN: mean percent clear nail; CO: complete cure rate; CR: clinical response rate; D: mean diameter of inhibition zone (mm); E: efficacy rate; HCl: hydrochloride; KOH: potassium hydroxide; M: mycological cure rate; MR: mycological recurrence rate; N: no clinical improvement rate; S: stigma; N/a: not applicable; NC: negative culture; O: decrease in onychomycosis severity index score; OP: overall problem; OSI: onychomycosis severity index score; PA: physical activities problems; PS: patient satisfaction; R: recurrence rate; RL: relapse rate; S: stigma; SB: symptom bothersomeness; SCIO: Scoring Clinical Index for Onychomycosis; SF: symptom frequency; TS: treatment satisfaction. * Significant difference between treatment groups. † Studies showing significant benefit of combination therapy over monotherapy.